Unique Statistics:

open-access license: This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.5/), which permits unrestrictive use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Stress tasks are used to induce sympathetic nervous system (SNS) arousal. However, the efficacy and the patterns of SNS activation have not been systematically compared between different tasks.

Therefore, we analyzed SNS activation during the following stress tasks: Presentation of negative, positive, and – as a control – neutral affective pictures, Color-Word interference test (CWT), mental arithmetic under time limit, singing a song aloud, and giving a spontaneous talk. We examined 11 healthy subjects and recorded the following SNS parameters: Activation of emotional sweating by quantitative sudometry, skin vasoconstriction by laser-Doppler flowmetry, heart rate by ECG, blood pressure by determination of pulse wave transit time (PWTT), and electromyographic (EMG) activity of the trapezius muscle. Moreover, subjective stress ratings were acquired for each task using a visual analog scale.

All tasks were felt significantly stressful when compared to viewing neutral pictures. However, SNS activation was not reliable: Affective pictures did not induce a significant SNS response; singing, giving a talk and mental arithmetic selectively increased heart rate and emotional sweating. Only the CWT globally activated the SNS. Regarding all tasks, induction of emotional sweating, increase of heart rate and blood pressure significantly correlated with subjective stress ratings, in contrast to EMG and skin vasoconstriction.

Our results show that the activation of the SNS widely varies depending on the stress task. Different stress tasks differently activate the SNS, which is an important finding when considering sympathetic reactions - in clinical situations and in research.

INTRODUCTION

Sympathetic activation (e.g. by stress) is part of our daily life. An excessive activity of the sympathetic nervous system (SNS) might underlie different stress-related disorders. It is important to notice that these stress-related disorders are diverse; they might be serious like hypertension [1], annoying like stress-related myalgic pain [2, 3], or harmless like hyperhidrosis or flushing [4]. In contrast differential activation of the SNS in the lab is usually neglected. Only the difference between thermoregulatory and emotional SNS activation is commonly accepted. Thermoregulatory activation (e.g. by cold environment) activates vasoconstriction but inhibits sweating while emotional stimuli activate both. Only few studies have addressed the emotional activation of the SNS in detail.

Standard emotional stimuli which have been used in experimental studies to induce SNS activation comprise the international affective picture system (IAPS [5]) assembly [6, 7]. It has been shown that IAPS-related changes of SNS activity depend on valence of the pictures [8] and on general levels of individual anxiety [9]. Therefore, gender-specific versions of the picture system have been generated [10]. The Color-Word interference test (CWT) [11] is another task which has been repeatedly used in stress research [12-15]. In previous studies it has been shown that task pacing (self-paced vs. automatically paced), task speed [16], and response mode affected SNS activation [17]. Less common stress tasks are forcing participants to accomplish mental arithmetic under time limit [18, 19], singing a song aloud or giving a spontaneous talk to an audience [20, 21].

Undoubtedly, all these tasks induce SNS activation in general. However, it is less clear whether they differentially activate specific subcomponents of the SNS (e.g. blood pressure, heart rate, sweating). In the present study, we therefore analysed SNS activation in detail during different tasks. A finding of task-dependent SNS activation patterns would demonstrate that stress responses might be more specific than commonly assumed. This study was designed not only to improve our understanding of SNS function but also to facilitate comprehension and comparability of different studies focussing on SNS activation.

SUBJECTS AND METHODS

Subjects

We examined 11 young healthy volunteers (median age 24 years, range 22-29 years; 5 men, 6 women). None of them had a history of previous autonomic disease (e.g. diabetes mellitus) or took any medication which might influence the autonomic nervous system. Moreover, there was no evidence of hypertension in any subject. All subjects abstained from smoking and drinking caffeine on the day of investigation. Informed consent was obtained from all subjects and the study adhered to the tenets of the Declaration of Helsinki. The study was approved by the local ethics committee.

Volunteers rested in a supine position and were asked to perform the different stress tasks as described below. Room temperature (24°C) and humidity (50% relative humidity) were controlled, all subjects acclimatised for one hour. At the end of acclimatisation, skin temperature at the finger tips was measured using an infrared thermometer and was found to be above 30°C in any subject.

Sympathetic Arousals (Stress Tasks)

24 affective pictures with negative valence and 24 pictures with positive valence were selected from the international affective picture system (IAPS) [5] (see appendix for numbers of IAPS). The picture assemblies were different for men and women. 24 neutral pictures served as control. The pictures were presented with a duration of five seconds for each picture using a Powerpoint® slide show. Since spontaneous arousal while viewing neutral pictures might be better controlled than during baseline condition, SNS parameters of all stress tasks were compared to viewing neutral pictures in a separate analysis (see below).

The Color-Word interference test (CWT) used in our study was automatically paced. Color words written in a different color were presented on a PC screen every 2 seconds and the subjects had to indicate the color of the presented word (not the meaning of the word) verbally. Responses were automatically recorded.

The mental arithmetic task consisted of a visually presented subtraction calculation exercise with a multiple choice solution. Response was given verbally.

As a fourth task, subjects had to give a spontaneous talk to the lab personnel for two minutes. The topic of the talk (i.e. death penalty) was previously unknown.

Finally, all subjects had to sing a German children’s song aloud to the examiners. The text was presented in words, singing was also performed for two minutes.

Sympathetic Activation Parameters

Cardio–vascular parameters were registered with a FAN-device (Schwarzer, Germany). We extracted heart rate and pulse wave transit time (PWTT) from the FAN data. PWTT is a surrogate for arterial blood pressure [22]. The analysis of parameters indicating heart rate variability was inappropriate since 1) recording time was too short and 2) these parameters are often affected by breathing. Intentional breathing changes occurred during talking or singing, but this does not necessarily reflect autonomic activation.

Emotional sweating was measured using quantitative hygrometry [23]. In brief, sweat capsules were affixed to palms and constantly streamed by dry nitrogen. Humidity from sweat glands was measured downstream by capacitance hygrometry. For quantification, curves were intregrated, the area under the curve (AUC) for the respective period was computed and compared to the AUC of a baseline [23].

Surface electromyography (EMG) of the trapezius muscle was recorded by a Pathway MR-20-EMG (Prometheus Group, Dover, New Hampshire, USA). Electrodes were placed at 2/3 of the distance between vertebra prominens and acromion. Employing Synergy 3-D software (The Prometheus Group, Dover, New Hampshire, USA) EMG signals were rectified and then integrated to yield EMG sum activity.

Peripheral vasoconstriction was determined by measuring skin blood flow at the fingertips of the second finger employing the single point mode of a laser Doppler imager (LDI, Moor Instruments Limited, London, UK) as previously described [24]. In order to avoid movement artefacts, the forearm was fixed in a splint. Sampling frequency of the LDI was 20 Hz, time constant was set to 0.1 s, and distance to skin was 50 cm. Laser signals were further processed using dedicated software (moorLDI SPM 3.01; Moor Instruments, London, UK) and expressed as flux values (FV).

As all of these parameters regularly show fluctuations depending on the actual state of arousal, we computed difference values between the stress tasks, which lasted 120 seconds, and the mean values during a baseline period of 30 seconds before each single task.

Special care was taken that all sympathetic parameters returned to baseline between subsequent tasks.

In order to exclude differences of fitness, personality, and hormonal status, all known to affect SNS activation, we focussed on within-subject variability of SNS response. Thereby, influence of individual variability was minimized.

Study Design

The stress tasks were presented to the subjects in a randomised order; each task was performed only once in order to avoid adaptation. Choosing a randomised order we avoided the possibility of a higher state of arousal at the beginning of the experiment. The duration of each task was exactly two minutes. Between the tasks, participants were allowed to rest for at least five minutes. Directly after each stress task subjects rated subjective stressfulness of the preceding task on a 10 cm visual analog scale ranging from no (0) to maximal imaginable stress (10).

Examination was performed by MF and TP. TP recruited the subjects and knew them, which reduced unspecific arousal.

Statistical Analysis

Statistical analyses were performed using the software package “SPSS 12.0 for windows” (SPSS Inc., Chicago, Illinois, USA). In the first analyses, we compared differences between baseline and SNS responses of the different stress tasks. For this purpose we used a within-subject ANOVA and post-hoc t-tests. The same type of ANOVA was employed to compare the different tasks to viewing “neutral” pictures, which was defined as the control condition in our study. Correlation between mean variables was assessed by computing Spearman rank order correlations. Data are presented as mean +/- standard error of the mean (SEM). Statistical significance was assumed for p < 0.05.

In a first step, we correlated the individual stress ratings (n=11 subjects) during all tasks with the different sympathetic parameters. In the whole correlation matrix (7 tasks x 5 parameters) only three correlations were significant: Between stress ratings and PWTT during viewing neutral pictures (r=0.72, p < 0.05), between stress ratings and PWTT during singing (r=0.73, p < 0.05), and between stress ratings and LDI vasoconstriction during giving a talk (r=0.86, p <0.01).

In the second step, we analyzed whether subjective stress affected sympathetic activation on a group level. The mean stress ratings of the different tasks (n=7) were compared to the mean of the sympathetic activation parameters. As shown in Fig. (3), activation of emotional sweating (r=0.89, p < 0.01), acceleration of heart rate (r=0.93, p < 0.01) and reduction of PWTT (r=0.79, p < 0.05) significantly correlated with subjective stress ratings. Only trapezius EMG and skin vasoconstriction remained insignificant.

DISCUSSION

The adaptive stress response counteracts intrinsic or extrinsic threats to homeostasis. Examples are arousal or alertness [25]. One component in the complex concert of human stress response is activation of the sympathetic nervous system (SNS). It is widely believed that SNS activity during stress is changed in a global fashion - by premotor neurons in hypothalamus and brainstem, which induce sympathetic responses in a simultaneous and parallel way [26]. However, if stress becomes chronic, it becomes responsible for a variety of very different diseases and there is no indication for one common “stress disease”. Nevertheless, in the lab, stress tasks are used “uncritically” in order to activate the sympathetic nervous system, for example in imaging studies [27], although there have already been indications that the SNS response might be differentiated [28, 29]. Therefore, the present investigation aimed to assess sympathetic responses in more depth. We found that all common stress tasks under investigation activated the SNS. However, the extent and the pattern of SNS activation varied significantly. Moreover, we also found that only some SNS parameters significantly correlated with stress perception while others did not show a graded response.

The standardization of investigation and within-subject design of our study obviously reduced variability of sympathetic activation. Therefore, we are confident to have identified characteristic intra-individual patterns of SNS activation, even though the number of subjects in our study was small. Nevertheless, this should be taken into account and preclude generalizing our results to different cohorts.

The Different Components of Sympathetic Activation During Stress Tasks

Our results indicate that the CWT [30], albeit subjectively only moderately stressful, most robustly activates the components of the SNS under investigation. Moreover, the CWT is the only test, which activates the SNS even in addition to viewing neutral IAPS pictures, which serves as “control” condition in our study. This finding is mainly in accordance with previous studies [13, 31], which found the CWT to induce increased heart rate and decreased heart rate variability [17, 32]. Our results indicate that the CWT additionally increases blood pressure, induces emotional sweating and skin vasoconstriction, and activates trapezius muscles. This means, CWT might be the most recommended task when the origin of different SNS components in the brain e.g. by functional imaging – are to be investigated in detail. The other tests, even if perceived as more stressful, activated the SNS less reliably. For example, giving a talk did not significantly induce vasoconstriction, mental arithmetic, albeit subjectively most stressful [19], did not increase trapezius muscle activity. When compared to neutral affective pictures, an increase of SNS activity during mental arithmetic was only found for emotional sweating and heart rate.

IAPS Pictures are Weak SNS Stimuli

Presentation of negative or positive affective pictures is a generally established stress task [33]. However, our results indicate that pictures of both valences induced only minor SNS activation. The only parameter, which was significantly different from baseline was skin vasoconstriction. Moreover, there was no difference of any SNS parameter between neutral and positive or negative affective pictures. This is in contrast to a previous study, which reported changes in skin conductance (a surrogate for emotional sweating) during the presentation of affective pictures [33]. It might be speculated that those pictures evoked higher levels of stress than in our study. Interestingly, affective pictures in the aforementioned study did not induce EMG activity or increase of heart rate, which supports our results.

Likely, the context of presentation affects SNS activation of affective pictures. An increase of heart rate during presentation of affective pictures has been observed - if the subjects focused on the heartbeats [34], or if erotic pictures were shown to men but not to women [35]. The main proportion of the pictures did not induce SNS changes – as in the present study. A more detailed investigation of the SNS response to affective pictures found an initial decrease and a later increase of heart rate during presentation [36]. Since we did not analyse this aspect of SNS changes, we might have missed these minor SNS activations. However, this does not change our assumption that affective pictures only minimally activate the SNS although they are considered as stressful.

Which SNS Activation Best Reflects Stress?

Perception of stress is complex and varies substantially between individuals [37]. Stress initiates the cognitive evaluation of a situation, it affects behaviour and decision making, induces humoral responses and finally activates the SNS [25]. Perception of SNS activation might subsequently even reinforce stress perception [38]. Given the complexity of the stress response, it is astonishing that we were able to show that subjective perception of stress linearly correlated with heart rate, blood pressure and emotional sweating. This result is in particular important since many functional brain imaging studies investigating the stress response used correlation analysis between stressfulness and brain activation in order to dissect brain areas, for example cognitive evaluation or decision making [39]. Our results now admonish to consider that any brain activation, which is identified by correlation analysis, might be also due to neuronal correlates of SNS activation. Functional imaging studies investigating stress should therefore be carefully controlled – at least with respect to the SNS parameters mentioned above. Muscle and vasoconstrictor activity did not show a graded response as a function of subjective stress perception; they seem to respond in an all-or-nothing fashion. In previous studies, if two categories of subjects or stress tasks have been compared – one category with low and one with high stress ratings – SNS activation was significantly stronger if high stress was perceived [40, 41]. These previous results strongly support our statements.

In conclusion, our study demonstrates that activation of the SNS during stress tasks might vary significantly – depending on the task and the SNS parameter under investigation. Our results favour a more differentiated appreciation of sympathetic reactions – in clinical situations and in research.

ACKNOWLEDGEMENT

This study was supported by the Deutsche Forschungsgemeinschaft Bi-579/1 and Bi-579/4. This study contains essential parts of the MD thesis of T. Purat, which will be submitted to the Faculty of Medicine, Johannes Gutenberg-University, Mainz, Germany.

About the Editor

Biography of George Perry

George Perry is a neuroscientist recognized in the field of Alzheimer's disease research particularly for his work in oxidative stress. Dr. Perry has studied at many universities and holds multiple degrees including a Bachelor of Arts degree in Zoology from the University of California Santa Barbara and a PhD in Marine Biology from the Scripps Institution of Oceanography at San Diego. He is distinguished as one of the top Alzheimer’s disease researchers by Expertscape with over 1000 publications, more than 70,000 citations (H=141), one of the top 100 most-cited scientists in Neuroscience & Behavior and one of the top 25 scientists in free radical research. Dr. Perry is a Semmes Foundation Distinguished University Chair in Neurobiology and is an active participant in many other scientific associations. He is an elected member of the Academies of Sciences of Mexico, Portugal, and Spain. In addition, Perry is an Editor of numerous scientific journals.

Quick Links

Indexing Agencies

Press Release

Join Our Editorial Board

News release date: March 29, 2018

Description:

The Open Neurology Journal is an Open Access online journal, which publishes research articles, reviews, letters, case reports and guest-edited single topic issues in all areas of neurology and neurological disorders. Bentham Open ensures speedy peer review process and accepted papers are published within 2 weeks of final acceptance.

The Open Neurology Journal is committed to ensuring high quality of research published. We believe that a dedicated and committed team of editors and reviewers make it possible to ensure the quality of the research papers. The overall standing of a journal is in a way, reflective of the quality of its Editor(s) and Editorial Board and its members.

The Open Neurology Journal is seeking energetic and qualified researchers to join its editorial board team as Editorial Board Members or reviewers.

The essential criteria to become Editorial Board Members of The Open Neurology Journal are as follows:

Experience in neurology and neurological disorders with an academic degree.

At least 20 publication records of articles and /or books related to the field of neurology and neurological disorders or in a specific research field.

Proficiency in English language.

The Roles of Editorial Board Member are to:

Offer advice on journals’ policy and scope.

Submit or solicit at least one article for the journal annually.

Contribute and/or solicit Guest Edited thematic issues to the journal in a hot area (at least one thematic issue every two years).

Peer-review of articles for the journal, which are in the area of expertise (2 to 3 times per year).

If you are interested in becoming our Editorial Board member, please submit the following information to info@benthamopen.com. We will respond to your inquiry shortly.

Email subject: Editorial Board Member Application

Your name

Email address

Telephone

City, State, Country

Name of your institution

Department or Division

Website of institution

Your title or position

Your highest degree

Complete list of publications and h-index

Interested field(s)

Testimonials

"Open access will revolutionize 21st century knowledge work and accelerate the diffusion of ideas and evidence that support just in time learning and the evolution of thinking in a number of disciplines."

. —Daniel Pesut. (Indiana University School of Nursing, USA).

"It is important that students and researchers from all over the world can have easy access to relevant, high-standard and timely scientific information. This is exactly what Open Access Journals provide and this is the reason why I support this endeavor."

"Publishing research articles is the key for future scientific progress. Open Access publishing is therefore of utmost importance for wider dissemination of information, and will help serving the best interest of the scientific community."

. —Patrice Talaga. (UCB S.A., Belgium).

"Open access journals are a novel concept in the medical literature. They offer accessible information to a wide variety of individuals, including physicians, medical students, clinical investigators, and the general public. They are an outstanding source of medical and scientific information."

. —Jeffrey M. Weinberg. (St. Luke's-Roosevelt Hospital Center, USA).

"Open access journals are extremely useful for graduate students, investigators and all other interested persons to read important scientific articles and subscribe scientific journals. Indeed, the research articles span a wide range of area and of high quality. This is specially a must for researchers belonging to institutions with limited library facility and funding to subscribe scientific journals."

. —Debomoy K. Lahiri. (Indiana University School of Medicine, USA).

"Open access journals represent a major break-through in publishing. They provide easy access to the latest research on a wide variety of issues. Relevant and timely articles are made available in a fraction of the time taken by more conventional publishers. Articles are of uniformly high quality and written by the world's leading authorities."

. —Robert Looney. (Naval Postgraduate School, USA).

"Open access journals have transformed the way scientific data is published and disseminated: particularly, whilst ensuring a high quality standard and transparency in the editorial process, they have increased the access to the scientific literature by those researchers that have limited library support or that are working on small budgets."

. —Richard Reithinger. (Westat, USA).

"Not only do open access journals greatly improve the access to high quality information for scientists in the developing world, it also provides extra exposure for our papers."

. —J. Ferwerda. (University of Oxford, UK).

"Open Access 'Chemistry' Journals allow the dissemination of knowledge at your finger tips without paying for the scientific content."

. —Sean L. Kitson. (Almac Sciences, Northern Ireland).

"In principle, all scientific journals should have open access, as should be science itself. Open access journals are very helpful for students, researchers and the general public including people from institutions which do not have library or cannot afford to subscribe scientific journals. The articles are high standard and cover a wide area."

. —Hubert Wolterbeek. (Delft University of Technology, The Netherlands).

"The widest possible diffusion of information is critical for the advancement of science. In this perspective, open access journals are instrumental in fostering researches and achievements."

. —Alessandro Laviano. (Sapienza - University of Rome, Italy).

"Open access journals are very useful for all scientists as they can have quick information in the different fields of science."

. —Philippe Hernigou. (Paris University, France).

"There are many scientists who can not afford the rather expensive subscriptions to scientific journals. Open access journals offer a good alternative for free access to good quality scientific information."

"Open access journals have become a fundamental tool for students, researchers, patients and the general public. Many people from institutions which do not have library or cannot afford to subscribe scientific journals benefit of them on a daily basis. The articles are among the best and cover most scientific areas."

. —M. Bendandi. (University Clinic of Navarre, Spain).

"These journals provide researchers with a platform for rapid, open access scientific communication. The articles are of high quality and broad scope."

. —Peter Chiba. (University of Vienna, Austria).

"Open access journals are probably one of the most important contributions to promote and diffuse science worldwide."

"Open access journals make up a new and rather revolutionary way to scientific publication. This option opens several quite interesting possibilities to disseminate openly and freely new knowledge and even to facilitate interpersonal communication among scientists."

. —Eduardo A. Castro. (INIFTA, Argentina).

"Open access journals are freely available online throughout the world, for you to read, download, copy, distribute, and use. The articles published in the open access journals are high quality and cover a wide range of fields."

. —Kenji Hashimoto. (Chiba University, Japan).

"Open Access journals offer an innovative and efficient way of publication for academics and professionals in a wide range of disciplines. The papers published are of high quality after rigorous peer review and they are Indexed in: major international databases. I read Open Access journals to keep abreast of the recent development in my field of study."

. —Daniel Shek. (Chinese University of Hong Kong, Hong Kong).

"It is a modern trend for publishers to establish open access journals. Researchers, faculty members, and students will be greatly benefited by the new journals of Bentham Science Publishers Ltd. in this category."